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Plasmodium vivax
Image by Mae Melvin
Genomic research suggests the malaria parasite Plasmodium vivax is evolving rapidly to adapt to conditions in different geographic locations.
Researchers studied more than 200 parasite samples from across the Asia-Pacific region and found that P vivax has evolved differently in different areas.
The team identified substantial differences in the frequency of copy number variations (CNVs) in samples from western Thailand, western Cambodia, and Papua Indonesia.
They believe this is a result of the different antimalarial drugs used in these regions.
The researchers described this work in Nature Genetics.
“For so long, it’s not been possible to study P vivax genomes in detail, on a large-scale, but now we can, and we’re seeing the effect that drug use has on how parasites are evolving,” said study author Dominic Kwiatkowski, of the Wellcome Trust Sanger Institute in the UK.
He and his colleagues studied the genomes of 228 parasite samples, identifying the strains carried by each patient and revealing their infection history. Most samples came from Southeast Asia (Thailand, Cambodia, Vietnam, Laos, Myanmar, and Malaysia) and Oceania (Papua Indonesia and Papua New Guinea), but the team also studied samples from China, India, Sri Lanka, Brazil, and Madagascar.
The researchers performed detailed population genetic analyses using 148 samples from western Thailand, western Cambodia, and Papua Indonesia. This revealed CNVs in 9 regions of the core genome, and the frequency of the 4 most common CNVs varied greatly according to geographical location.
The first common CNV was a 9-kb deletion on chromosome 8 that includes the first 3 exons of a gene encoding a cytoadherence-linked asexual protein. The CNV was present in 73% of Papua Indonesia samples, 6% of western Cambodia samples, and 3% of western Thailand samples.
The second common CNV was a 7-kb duplication on chromosome 6 that encompasses pvdbp, the gene that encodes the Duffy-binding protein, which mediates P vivax’s invasion of erythrocytes. It was present in 5% of Papua Indonesia samples, 35% of western Cambodia samples, and 25% of western Thailand samples.
The third common CNV was a 37-kb duplication on chromosome 10 that includes pvmdr1, which has been associated with resistance to mefloquine and is homologous to the pfmdr1 amplification responsible for mefloquine resistance in P falciparum. This CNV was only present in samples from western Thailand.
The fourth common CNV was a 3-kb duplication on chromosome 14 that includes the gene PVX_101445. It was found only in Papua Indonesia samples.
“Our study shows that the strongest evidence of evolution is in Papua, Indonesia, where resistance of P vivax to chloroquine is now rampant,” said Ric Price, MD, of the University of Oxford in the UK.
“These data provide crucial information from which we can start to identify the mechanisms of drug resistance in P vivax.”
“We can see in the genome that drug resistance is a huge driver for evolution,” added Richard Pearson, PhD, of the Wellcome Trust Sanger Institute.
“Intriguingly, in some places, this process appears to be happening in response to drugs used primarily to treat a different malaria parasite, P falciparum. Although the exact cause isn’t known, this is a worrying sign that drug resistance is becoming deeply entrenched in the parasite population.”
The researchers said there are a few possible reasons why P vivax may be evolving to evade drugs used against P falciparum.
Many people carry mixed infections of both species of parasite, so, in treating one species, the other automatically gets exposed to the drug. Another culprit may be unsupervised drug use—where many people take the most readily available, rather than the most suitable, antimalarial drug.
Another finding from this study was that, when the researchers identified patients who were carrying multiple strains of parasite, the genomic data made it possible to determine how closely the different strains were related to one another.
“This means that we can now start to pull apart the genetic complexity of individual Plasmodium vivax infections and work out whether the parasites came from one or more mosquito bites,” Kwiatkowski said. “It provides a way of addressing fundamental questions about how P vivax is transmitted and how it persists within a community and, in particular, about the biology of relapsing infections.” 
Plasmodium vivax
Image by Mae Melvin
Genomic research suggests the malaria parasite Plasmodium vivax is evolving rapidly to adapt to conditions in different geographic locations.
Researchers studied more than 200 parasite samples from across the Asia-Pacific region and found that P vivax has evolved differently in different areas.
The team identified substantial differences in the frequency of copy number variations (CNVs) in samples from western Thailand, western Cambodia, and Papua Indonesia.
They believe this is a result of the different antimalarial drugs used in these regions.
The researchers described this work in Nature Genetics.
“For so long, it’s not been possible to study P vivax genomes in detail, on a large-scale, but now we can, and we’re seeing the effect that drug use has on how parasites are evolving,” said study author Dominic Kwiatkowski, of the Wellcome Trust Sanger Institute in the UK.
He and his colleagues studied the genomes of 228 parasite samples, identifying the strains carried by each patient and revealing their infection history. Most samples came from Southeast Asia (Thailand, Cambodia, Vietnam, Laos, Myanmar, and Malaysia) and Oceania (Papua Indonesia and Papua New Guinea), but the team also studied samples from China, India, Sri Lanka, Brazil, and Madagascar.
The researchers performed detailed population genetic analyses using 148 samples from western Thailand, western Cambodia, and Papua Indonesia. This revealed CNVs in 9 regions of the core genome, and the frequency of the 4 most common CNVs varied greatly according to geographical location.
The first common CNV was a 9-kb deletion on chromosome 8 that includes the first 3 exons of a gene encoding a cytoadherence-linked asexual protein. The CNV was present in 73% of Papua Indonesia samples, 6% of western Cambodia samples, and 3% of western Thailand samples.
The second common CNV was a 7-kb duplication on chromosome 6 that encompasses pvdbp, the gene that encodes the Duffy-binding protein, which mediates P vivax’s invasion of erythrocytes. It was present in 5% of Papua Indonesia samples, 35% of western Cambodia samples, and 25% of western Thailand samples.
The third common CNV was a 37-kb duplication on chromosome 10 that includes pvmdr1, which has been associated with resistance to mefloquine and is homologous to the pfmdr1 amplification responsible for mefloquine resistance in P falciparum. This CNV was only present in samples from western Thailand.
The fourth common CNV was a 3-kb duplication on chromosome 14 that includes the gene PVX_101445. It was found only in Papua Indonesia samples.
“Our study shows that the strongest evidence of evolution is in Papua, Indonesia, where resistance of P vivax to chloroquine is now rampant,” said Ric Price, MD, of the University of Oxford in the UK.
“These data provide crucial information from which we can start to identify the mechanisms of drug resistance in P vivax.”
“We can see in the genome that drug resistance is a huge driver for evolution,” added Richard Pearson, PhD, of the Wellcome Trust Sanger Institute.
“Intriguingly, in some places, this process appears to be happening in response to drugs used primarily to treat a different malaria parasite, P falciparum. Although the exact cause isn’t known, this is a worrying sign that drug resistance is becoming deeply entrenched in the parasite population.”
The researchers said there are a few possible reasons why P vivax may be evolving to evade drugs used against P falciparum.
Many people carry mixed infections of both species of parasite, so, in treating one species, the other automatically gets exposed to the drug. Another culprit may be unsupervised drug use—where many people take the most readily available, rather than the most suitable, antimalarial drug.
Another finding from this study was that, when the researchers identified patients who were carrying multiple strains of parasite, the genomic data made it possible to determine how closely the different strains were related to one another.
“This means that we can now start to pull apart the genetic complexity of individual Plasmodium vivax infections and work out whether the parasites came from one or more mosquito bites,” Kwiatkowski said. “It provides a way of addressing fundamental questions about how P vivax is transmitted and how it persists within a community and, in particular, about the biology of relapsing infections.”
Plasmodium vivax
Image by Mae Melvin
Genomic research suggests the malaria parasite Plasmodium vivax is evolving rapidly to adapt to conditions in different geographic locations.
Researchers studied more than 200 parasite samples from across the Asia-Pacific region and found that P vivax has evolved differently in different areas.
The team identified substantial differences in the frequency of copy number variations (CNVs) in samples from western Thailand, western Cambodia, and Papua Indonesia.
They believe this is a result of the different antimalarial drugs used in these regions.
The researchers described this work in Nature Genetics.
“For so long, it’s not been possible to study P vivax genomes in detail, on a large-scale, but now we can, and we’re seeing the effect that drug use has on how parasites are evolving,” said study author Dominic Kwiatkowski, of the Wellcome Trust Sanger Institute in the UK.
He and his colleagues studied the genomes of 228 parasite samples, identifying the strains carried by each patient and revealing their infection history. Most samples came from Southeast Asia (Thailand, Cambodia, Vietnam, Laos, Myanmar, and Malaysia) and Oceania (Papua Indonesia and Papua New Guinea), but the team also studied samples from China, India, Sri Lanka, Brazil, and Madagascar.
The researchers performed detailed population genetic analyses using 148 samples from western Thailand, western Cambodia, and Papua Indonesia. This revealed CNVs in 9 regions of the core genome, and the frequency of the 4 most common CNVs varied greatly according to geographical location.
The first common CNV was a 9-kb deletion on chromosome 8 that includes the first 3 exons of a gene encoding a cytoadherence-linked asexual protein. The CNV was present in 73% of Papua Indonesia samples, 6% of western Cambodia samples, and 3% of western Thailand samples.
The second common CNV was a 7-kb duplication on chromosome 6 that encompasses pvdbp, the gene that encodes the Duffy-binding protein, which mediates P vivax’s invasion of erythrocytes. It was present in 5% of Papua Indonesia samples, 35% of western Cambodia samples, and 25% of western Thailand samples.
The third common CNV was a 37-kb duplication on chromosome 10 that includes pvmdr1, which has been associated with resistance to mefloquine and is homologous to the pfmdr1 amplification responsible for mefloquine resistance in P falciparum. This CNV was only present in samples from western Thailand.
The fourth common CNV was a 3-kb duplication on chromosome 14 that includes the gene PVX_101445. It was found only in Papua Indonesia samples.
“Our study shows that the strongest evidence of evolution is in Papua, Indonesia, where resistance of P vivax to chloroquine is now rampant,” said Ric Price, MD, of the University of Oxford in the UK.
“These data provide crucial information from which we can start to identify the mechanisms of drug resistance in P vivax.”
“We can see in the genome that drug resistance is a huge driver for evolution,” added Richard Pearson, PhD, of the Wellcome Trust Sanger Institute.
“Intriguingly, in some places, this process appears to be happening in response to drugs used primarily to treat a different malaria parasite, P falciparum. Although the exact cause isn’t known, this is a worrying sign that drug resistance is becoming deeply entrenched in the parasite population.”
The researchers said there are a few possible reasons why P vivax may be evolving to evade drugs used against P falciparum.
Many people carry mixed infections of both species of parasite, so, in treating one species, the other automatically gets exposed to the drug. Another culprit may be unsupervised drug use—where many people take the most readily available, rather than the most suitable, antimalarial drug.
Another finding from this study was that, when the researchers identified patients who were carrying multiple strains of parasite, the genomic data made it possible to determine how closely the different strains were related to one another.
“This means that we can now start to pull apart the genetic complexity of individual Plasmodium vivax infections and work out whether the parasites came from one or more mosquito bites,” Kwiatkowski said. “It provides a way of addressing fundamental questions about how P vivax is transmitted and how it persists within a community and, in particular, about the biology of relapsing infections.”